United States Patent 7,256,310 (Levalbuterol L-tartrate) Scope, Claims, and US Patent Landscape
US Patent 7,256,310 is a formulation-and-crystallization centered patent family focused on levalbuterol L-tartrate in a crystalline state with controlled particle morphology (micronized, needle-like), plus specific inhalation delivery embodiments using a metered dose inhaler with 1,1,1,2-tetrafluoroethane (HFA-134a) as propellant and ethanol as a co-solvent in defined ranges. It also claims a crystallization and processing route that directly ties downstream morphology to selected solvent and crystallization/drying conditions.
What does the patent claim at the product level?
The independent claim set is not provided in your excerpt; however, the full provided claim text shows a consistent architecture:
1) Substance definition (levalbuterol L-tartrate; crystalline form)
2) Morphology control (micronized; needle-like particles; crystal dimensions)
3) Formulation definition (a composition and inhalation formulations with propellant and optional excipients)
4) Device definition (metered dose inhaler with the claimed formulation in a canister and metering hardware)
5) Process and intermediates (crystallization from ethanolic solutions; drying/micronization to yield needle-like particles)
6) Use (bronchodilation methods; inhalation administration embodiments)
Core material claims
- Claim 1: Levalbuterol L-tartrate
- Claim 2: Levalbuterol L-tartrate in crystalline form
- Claim 3: Crystalline levalbuterol L-tartrate containing 0.3 to 0.7% ethanol
- Claims 4-5: Crystalline levalbuterol L-tartrate in micronized form as needle-like particles
- Claims 25-26: levalbuterol L-tartrate crystals obtained by process claims (18 and 24)
Formulation and excipient scope
- Claim 6: Pharmaceutical composition comprising claimed levalbuterol L-tartrate + pharmaceutically acceptable carrier
- Claims 7-11 (MDI-focused formulation):
- Claim 7: aerosol formulation adapted for a metered dose inhaler with:
- crystalline levalbuterol L-tartrate
- a propellant
- Claim 8: propellant is 1,1,1,2-tetrafluoroethane
- Claim 9: further comprises a surfactant
- Claim 10: further comprises a co-solvent
- Claim 11: co-solvent is ethanol
- Claims 12-14: an aerosol formulation with:
- crystalline levalbuterol L-tartrate crystals that are micronized, needle-like particles
- propellant
- Claim 13: propellant is 1,1,1,2-tetrafluoroethane
- Claim 14: further comprises 2 to 6% by weight ethanol
Metered dose inhaler claim scope
- Claim 15: MDI with canister containing aerosol formulation as defined in claim 7, plus metering valve and valve stem
- Claim 16: MDI with canister containing aerosol formulation as defined in claim 12, plus metering valve and valve stem
Dry powder / insufflator claim scope
- Claim 17: pharmaceutical composition adapted for administration using a dry powder inhaler or insufflator
Therapeutic method scope
- Claim 27: method of bronchodilation using effective amount of levalbuterol L-tartrate
- Claims 28-29 (inhalation morphology):
- Claim 28: micronized crystals administered by inhalation using a metered dose inhaler
- Claim 29: micronized crystals in needle-like particles form
What morphology, size, and residual solvent constraints are enforced?
Your excerpt contains both structural constraints (needle-like particles; micronized) and processing-linked constraints (crystallization and processing conditions that are meant to yield those particle attributes).
Direct morphology and residual solvent constraints (material claims)
- Needle-like particles: Claims 5, 12, 29
- Micronized: Claims 4, 12, 28-29
- Ethanol content in crystalline material: Claim 3 requires 0.3 to 0.7% ethanol
Processing conditions tied to crystal dimensions (process claims)
- Claim 20: crystallization conditions selected to provide crystals having:
- length 10 to 50 microns
- width 0.2 to 4 microns
Processing-to-morphology linkage
- Claim 23: crystallization and drying conditions selected so that after micronization the particles are needle-like
- Claim 24: an end-to-end process explicitly requiring:
- crystallization from levalbuterol + L-tartaric acid
- then drying and micronizing
- with conditions selected to yield needle-like particles after micronization
This structure creates a “tight coupling” between:
- what the final solid looks like (needle-like)
- what processing steps and conditions are used (ethanol-based solutions; selected crystallization/drying; micronization)
What formulation and delivery choices are required for infringement risk?
The inhalation portion is concentrated on an MDI with specific propellant and ethanol. That provides relatively concrete “design-around” levers for competitors, even though the patent also includes broader composition and method claims.
MDI aerosol formulation constraints
- Propellant must be 1,1,1,2-tetrafluoroethane:
- Co-solvent ethanol:
- Claims 11 (ethanol as co-solvent in claim 10 chain)
- Claim 14: ethanol 2 to 6% by weight (in the MDI embodiment tied to micronized needle-like crystals)
Surfactant optionality
- Claim 9: surfactant is included, but the claim is “further comprises,” meaning it is not strictly required in other claim chains. The surfactant requirement becomes relevant only if the asserted claim is the one reciting surfactant.
MDI hardware requirements
- For the MDI device claims, infringement depends on:
- a canister containing the claimed aerosol formulation
- a metering valve
- a valve stem
(Claims 15-16)
How broad is the claim set versus the specific invention?
US 7,256,310 appears to sit on the boundary between:
- composition of matter coverage (levalbuterol L-tartrate in crystalline form, micronized needle-like)
- formulation coverage (MDI aerosol with HFA-134a, ethanol co-solvent in defined amounts)
- process coverage (ethanol solvent crystallization; conditions yielding specific dimensions; drying and micronization)
- use coverage (bronchodilation method; inhalation via MDI with needle-like micronized crystals)
Breadth highlights
- Claim 1 and Claim 2 are broad as to how the compound is made and used, but they are anchored to levalbuterol L-tartrate and crystalline form.
- Claim 6 is a broad composition claim (active + carrier), but “infringement” depends on whether the accused product contains the claimed crystalline levalbuterol L-tartrate meeting the same definition.
Narrowing highlights
- Multiple claims narrow to:
- crystalline form containing 0.3 to 0.7% ethanol (Claim 3)
- micronized needle-like particles (Claims 4-5, 12, 29)
- propellant must be HFA-134a (Claims 8, 13)
- ethanol 2 to 6% by weight (Claim 14)
- crystal dimensions (Claim 20)
- and end-to-end process structures (Claims 24 and 18 chain)
These narrowing elements matter most for competitive portfolio strategy: formulations using different propellants or ethanol levels, or solids that do not meet the “needle-like” morphology and residual ethanol constraints, can fall outside the tight claim language.
What is the process scope and how tightly does it map to the final solid?
The process claims define an origin story from solution crystallization to dried/micronized morphology.
Crystallization and recovery
- Claim 18: combines:
- a solution of levalbuterol
- with a solution of L-tartaric acid
- then recover levalbuterol L-tartrate crystals
- Claim 19: solvent in each solution comprises ethanol
- Claim 20: crystallization conditions produce crystals with:
- length 10-50 microns
- width 0.2-4 microns
Downstream transformation to needle-like micronized particles
- Claim 23: crystals are dried and micronized, with conditions selected to afford needle-like particles after micronization
- Claim 24: crystallization + then drying and micronizing with conditions selected so that the resulting micronized solids are needle-like particles
Upstream API preparation pathway (R-benzylalbuterol hydrogenation)
- Claim 21: levalbuterol prepared by hydrogenating R-benzylalbuterol in presence of palladium on carbon
- Claim 22: hydrogenation conditions chosen to convert:
- at least 99.9% of R-benzylalbuterol
- without over-reduction of other functional groups
This ties the patent’s manufacturing narrative to a specific route for producing levalbuterol prior to salt formation.
Patent landscape implications (US competitive positioning)
Without access to the complete cited patent record in your input, the landscape section below focuses strictly on “landscape mechanics” that follow from the claim structure you provided: where competitors can face, and where they can avoid, overlap.
Hot-spot infringement pathways
1) Crystalline levalbuterol L-tartrate (claims 1-3) where residual ethanol matches 0.3-0.7%
2) Needle-like micronized solid for inhalation (claims 4-5, 12, 25-26, 29)
3) MDI formulation using HFA-134a (claims 7-8, 12-13)
4) Ethanol level in the MDI tied to needle-like micronized crystals (2-6% by weight, claim 14)
5) Process embodiments that generate needle-like micronized particles via:
- ethanolic solutions (claim 19)
- specific crystal size window (claim 20)
- drying and micronization conditions that preserve/produce needle-like morphology (claims 23-24)
Likely design-around levers
- Switch propellant away from 1,1,1,2-tetrafluoroethane (claims 8 and 13)
- Adjust ethanol co-solvent formulation so it does not meet “2 to 6% by weight” in the needle-like crystal MDI embodiment (claim 14)
- Change the solid-state morphology away from “needle-like particles” after micronization (claims 5, 12, 23-24, 29)
- Avoid the specific residual ethanol window in the crystalline salt (claim 3)
- Modify crystallization/drying/micronization parameters so crystal size and/or needle-like outcome does not meet claim language (claim 20 and 23-24)
Freedom-to-operate pressure points
- If an ANDA or branded product uses an MDI route that matches propellant and ethanol/co-solvent and uses solids that can be characterized as needle-like micronized particles, the infringement risk rises quickly across multiple claim families (material + formulation + device + method).
- If the product is a dry powder inhaler/insufflator, claim 17 provides some exposure, but the excerpt does not specify the particle morphology requirements in that branch beyond “adapted for administration,” so the risk analysis depends on which solid attribute the marketed product actually exhibits.
Key Takeaways
- US 7,256,310 is anchored on levalbuterol L-tartrate crystalline solids with micronized needle-like particle morphology and specific ethanol-related constraints (0.3-0.7% residual ethanol in the solid; 2-6% by weight ethanol in an MDI formulation branch).
- The tightest formulation coverage is for an MDI aerosol using 1,1,1,2-tetrafluoroethane (HFA-134a), with ethanol as a co-solvent and, in the narrow embodiment, with needle-like micronized crystals.
- The process claims enforce a linked pathway: ethanol-based crystallization from levalbuterol and L-tartaric acid, optional upstream hydrogenation conditions for the API, and drying plus micronization selected to yield needle-like particles; crystal dimensions are specified (10-50 µm length; 0.2-4 µm width).
- For competitor portfolio strategy, the most actionable design-around levers are propellant selection, ethanol level, and solid-state particle morphology/size outcomes after micronization.
FAQs
1) Which claim language most directly constrains particle morphology for inhalation?
Claims 4-5 (micronized needle-like particles), 12 (micronized needle-like particles in the MDI aerosol formulation), 23-24 (processing selected to afford needle-like particles after micronization), and 29 (needle-like micronized particles administered by MDI).
2) What ethanol specifications exist, and where do they apply?
The crystalline solid branch requires 0.3 to 0.7% ethanol (Claim 3). The MDI aerosol branch tied to needle-like micronized crystals requires ethanol 2 to 6% by weight (Claim 14) and specifies ethanol as co-solvent (Claim 11).
3) What propellant does the patent lock in for the MDI embodiments?
1,1,1,2-tetrafluoroethane is required in the MDI formulation claims (Claims 8 and 13).
4) Does the patent include a manufacturing process claim for crystallization?
Yes. Claims 18-20 cover crystallization from levalbuterol and L-tartaric acid, with ethanol as the solvent in each solution (Claim 19) and crystal dimensions (Claim 20). Claims 23-24 cover drying and micronization to yield needle-like particles.
5) Is there a device-level claim that targets metered dose inhalers?
Yes. Claims 15-16 cover an MDI with a canister containing the specific aerosol formulation, plus a metering valve and valve stem.
References
[1] United States Patent 7,256,310. Claims as provided in the prompt.
